Routine and Special Vaccinations in People With HIV.

Vaccinations are an important part of primary care for people with HIV (PWH) and can protect against viral hepatitis and some sexually transmitted infections, as well as respiratory bacterial and viral infections. Vaccinations for influenza, COVID-19, herpes zoster (shingles), hepatitis B, meningococcal disease, mpox, and human papillomavirus are recommended for PWH. Additionally, the Advisory Committee on Immunization Practices has released recommendations incorporating the newer formulations of the pneumococcal pneumonia and respiratory syncytial virus vaccines. Additional considerations for the timing of vaccinations are de-scribed, including whether to delay vaccination until improvement of the immune status. Live vaccines (other than nonreplicating) are contraindicated for PWH with CD4+ counts less than 200 cells/µL or uncontrolled HIV.

HIV and COVID-19: review of clinical course and outcomes.

Background:Understanding the relationship between HIV and SARS-CoV-2 has important public health implications.Objective:To summarize current research on COVID-19 among people with HIV (PWH) as published through 15 July 2021.Methods: We conducted a search of PubMed, Scopus, preprint databases (medRxiv, bioRxiv), and the references of publications found using key terms relevant to COVID-19 ('COVID-19' OR 'SARS-CoV-2' OR 'coronavirus') AND to HIV ('HIV' OR 'Human Immunodeficiency Virus' OR 'AIDS' OR 'Acquired Immunodeficiency Syndrome'). We summarized all articles that reported data or opinions on SARS-CoV-2 and HIV coinfection.Conclusions: Although many initial case series and cohort studies found no increased risk for SARS-CoV-2 infection or severe COVID-19 outcomes among PWH, recent studies have signaled an increased risk for severe COVID-19 disease progression even in the setting of well-controlled HIV. Whether this is due to the increased prevalence of comorbidities in PWH and other social determinants of health is unknown. These conflicting findings highlight the continued need for COVID-19 related research among PWH that addresses COVID-19 disease course as well as exacerbation of existing comorbidities already disproportionately represented among PWH.

Lower Mortality Associated With Adjuvant Corticosteroid Therapy in Non-HIV-Infected Patients With Pneumocystis jirovecii Pneumonia: A Single-Institution Retrospective US Cohort Study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids would reduce mortality in a cohort of HIV-negative PJP patients. METHODS: We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995 and 2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify mortality predictors. RESULTS: Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), and solid organ transplantation (10.7%). HIV-negative patients had higher rates and durations of mechanical ventilation and intensive care unit stay. Survival was significantly increased in HIV-negative patients receiving adjuvant corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (P = .034). In an adjusted multivariable model, no adjuvant corticosteroid use was associated with higher mortality (odds ratio, 13.5; 95% CI, 1.1-158.5; P = .039) regardless of HIV status. CONCLUSIONS: We found substantial mortality among HIV-negative patients with PJP, and adjuvant corticosteroid use was associated with decreased mortality. Response to corticosteroids is best established in HIV-infected patients, but emerging reports suggest a similar beneficial response in PJP patients without HIV infection. Further prospective studies may establish a more definitive role of the addition of corticosteroids among HIV-negative patients with PJP.

Opioid Use and Chronic Infections: The Value of Addressing the Syndemic in Correctional Settings Via Telemedicine Guidance and Broader Use of Long-Acting Medications.

In the United States, we are experiencing linked epidemics (a syndemic) of substance use disorders (SUDs) and infections associated with drug use, including unsafe injecting and unsafe sex in exchange for drugs or money. Current drug laws, together with risk-taking behavior among persons with SUDs, contribute to disproportionately high prevalences of these conditions in correctional settings. Detection and treatment of diseases with a high impact on public health are best addressed in the settings where such conditions are most prevalent (ie, jails and prisons for SUDs and chronic infections). The effectiveness, safety, cost of care. and public health impact of these conditions can be improved by means of broader screening and expanded access to specialty consultations through telemedicine/telehealth, along with broader use of long-acting medications for the treatment of human immunodeficiency virus and SUDs. Expanding telemedicine/telehealth, first for specialties which do not require advanced technology (eg, infectious diseases, addictions), can eventually lead to further advancements in correctional healthcare.

Cytomegalovirus myocarditis in solid organ transplant recipients: A case series and review of literature.

Cytomegalovirus (CMV) is a DNA virus of the Herpesviridae family and is estimated to affect 15%-30% of high-risk solid organ transplant recipients. Typical manifestations of CMV end-organ disease in this population include colitis, esophagitis, and pneumonitis, and myocarditis is a rarely reported manifestation. We describe two cases of CMV myocarditis in solid organ transplant recipients and review the literature regarding previously published cases of CMV myocarditis.

COVID-19 Serosurveillance May Facilitate Return-to-Work Decisions.

Public health measures are needed to resolve the novel coronavirus disease (COVID-19) pandemic, although a looming economic fallout merits close attention. Early safe reintroduction of immune individuals into the workforce may be essential to protecting the economic welfare of communities. Reverse transcriptase-polymerase chain reaction testing, our primary diagnostic tool to date, has sensitivity and timing concerns, owing to sampling/handling errors, as well as a complex virus-host interaction. Reverse transcriptase-polymerase chain reaction assays do not establish immune status once the virus has been cleared. Targeted serosurveillance for the determination of individuals' potential for transmissibility, particularly if paired with direct pathogen testing, may aid in "cleared for business" decision-making.

Hantavirus Infection with Renal Failure and Proteinuria, Colorado, USA, 2019.

In North America, hantaviruses commonly cause hantavirus pulmonary syndrome (HPS). Clinical descriptions of hantavirus-associated renal disease in the Americas are scarce. Herein, we discuss the case of a 61-year-old man whose predominant manifestations were acute kidney injury and proteinuria. Clinical recognition of renal signs in hantavirus infections can reduce risk for death.

Access to Specialty Services: Opportunities for Expansion of Telemedicine to Support Correctional Health Care in Colorado.

Introduction: The United States has the largest correctional population in the world and many inmates lack access to timely health care. Studies have shown that telemedicine could improve the situation in a practical and cost-effective fashion. We aimed to evaluate currently established services as well as any potential need for expansion of telemedicine within correctional settings in Colorado. Methods: We designed a prospective survey-based pilot study using mixed methods research techniques. Results: Colorado has 50 county jails, 19 prisons, and 3 private prison facilities. Of these, 46 correctional facilities (45 jails and the state prison) were contacted. Twenty responded (19 jails and the prison) representing 43.5% response rate. Only 10% did not have on-site health care providers available at all, 31.6% were already using telemedicine for some of their needs, 52.9% were "very interested," 5.9% "somewhat interested," 17.6% "not so interested," and 23.5% were "not at all interested" in further information regarding telemedicine services. Discussion: Our study as well as current literature suggest that telemedicine could serve to fill in certain gaps of care within correctional populations, especially for over-represented conditions (i.e., chronic infectious diseases, such as HIV and hepatitis C virus, substance use disorders, or mental health disorders). Conclusions: There is enthusiasm but also certain amount of skepticism among Colorado's jail administrators with respect to the implementation, or even the cost-effectiveness potential of telemedicine. Telemedicine in these settings may require individualized approach and enough creative flexibility to allow for nimble adjustments based on the constraints and needs of individual institutions.

Severe acute Q fever pneumonia complicated by presumed persistent localized Q fever endocarditis in a renal transplant recipient: A case report and review of the literature.

Q fever in solid organ transplant (SOT) recipients is rarely described in the medical literature. We present a case of severe acute Q fever pneumonia that evolved into persistent localized Q fever endocarditis in a renal transplant recipient.

Vaccination and Immunoprotection in People with HIV.

Vaccines play an important role in HIV primary care and are available for several sexually transmitted infections, including those caused by hepatitis A virus (HAV), hepatitis B virus (HBV), and human papillomavirus (HPV). HAV vaccination is increasingly important, given recent hepatitis A outbreaks and lack of immunity in many adults. A novel formulation of the hepatitis B vaccine shows promise in increasing rates of seroprotection. The Advisory Committee on Immunization Practices recommends the meningococcal conjugate vaccine for all individuals with HIV and has expanded the age range for administration of the HPV vaccine, recommending shared decision making about its administration in adults aged 27 to 45 years. This article summarizes a presentation by Steven C. Johnson, MD, at the International Antiviral Society-USA (IAS-USA) annual continuing education program held in New York, New York, in September 2019.

Examining Mortality to Identify Opportunities for Improved Care Among Adults with HIV in a Single Academic Medical Center.

Mortality for people living with HIV (PLWH) has dramatically decreased since the mid-1990s and the proportion of deaths attributable to non-AIDS-related conditions has increased. Deceased PLWH were identified from a single academic medical center through provider survey and electronic medical record query. Cause of death was determined using the Coding Causes of Death in HIV tool following review of available medical records. Chart review of comorbidities, demographics, laboratory values, and previous completion of screening tests for malignancies was conducted for deaths during the period of 2013-2017. The proportion of AIDS-related deaths decreased markedly between 1995 and 2017, while the proportion of deaths from non-AIDS malignancies increased. From 2013 to 2017, 30 of 121 deaths were attributed to AIDS-related conditions, 32 to non-AIDS malignancies, 14 to suicide/homicide or sudden death, 10 to cardiac causes, 28 to other non-HIV causes, and 7 to unknown causes. Those who died of non-AIDS-related malignancies were older than AIDS-related deaths [mean age 55.8 (7.6) vs. 47.3 (13.5), p value = .003]. Less than half of potentially eligible patients had documented colon cancer screening. The number of individuals dying from AIDS-related conditions has decreased significantly and non-AIDS-related causes, particularly non-AIDS-related malignancies, have become more prominent causes of death. As our patients age, a greater focus needs to be placed on management of comorbid illnesses and screening and prevention of malignancy.

Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy.

Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015.

Engagement-in-care during the first 5 years after HIV diagnosis: data from a cohort of newly HIV-diagnosed individuals in a large US city.

Initial descriptions of the HIV engagement continuum are limited by short-term follow-up and incomplete data. We evaluated engagement in a newly HIV-diagnosed cohort. Our goals were to assess long-term engagement-in-care, evaluate the effects of out-of-state migration on engagement estimates, and determine whether engagement has improved in more recently diagnosed individuals. This is a retrospective cohort study of individuals newly HIV-diagnosed at two large HIV care centers in the Denver metropolitan area from 2005 to 2009. Clinical data were obtained from three public HIV providers and two clinical trial groups. For statewide evaluation, we used mandated laboratory reporting databases for CD4 lymphocyte counts and HIV-1 RNA levels. From 2005 to 2009, 615 individuals were diagnosed with HIV. By 18 months after HIV diagnosis, 84% of the cohort had linked to care, 73% were retained in care, 49% were prescribed antiretroviral therapy, and 36% had viral suppression. By 5 years after HIV diagnosis, 55% of the cohort were retained in care, 37% had viral suppression, 15% had moved out of state, and 3% were deceased. When censoring for outmigration and death, 66% of the cohort were retained in care and 45% of the cohort had viral suppression 5 years after HIV diagnosis. Engagement-in-care 18 months after diagnosis was better in individuals diagnosed more recently. Retention in care declined while viral suppression increased over time after HIV diagnosis. Accounting for outmigration and death significantly increased estimates of engagement-in-care. Performance in the engagement continuum 18 months after diagnosis improved significantly in individuals more recently diagnosed with HIV.

Diagnostic tests for syphilis: New tests and new algorithms.

Syphilis is a sexually transmitted infection caused by Treponema pallidum. A total of 13,106 cases of primary and secondary syphilis were reported in the United States in 2011 and the rate of infection has increased in subgroups, particularly men who have sex with men. The disease is mainly diagnosed through clinical findings and serologic testing. However, no single serologic test of syphilis is sufficient. Hence, the serologic diagnosis of syphilis requires the detection of 2 types of antibodies (nontreponemal antibodies and treponemal antibodies). The paradigm in syphilis testing has recently shifted in many centers to screen with a treponemal antibody test, reflexing to a nontreponemal test if the treponemal antibody test is positive. This reverse of the traditional algorithm may not be widely recognized among clinicians.

Initial linkage and subsequent retention in HIV care for a newly diagnosed HIV-infected cohort in Denver, Colorado.

This is a retrospective cohort study of 352 newly diagnosed HIV-infected individuals in Denver, from 2005 to 2007. Utilizing data from 3 health care systems, 2 clinical trials units, and statewide Colorado HIV laboratory reporting databases, we tracked initial linkage to HIV care, retention in care, loss to follow-up, and transitions between HIV care providers. After more than 2.6 years of follow-up, 256 (73%) individuals linked to HIV care within 180 days. Of the 301 individuals who eventually linked to care, 168 (56%) had at least one 180-day gap in care, while 49 (16%) had a 360-day gap. Transitions in care were common, with 131 (37%) individuals accessing care from 2 different providers and 15% having evidence of living outside of Colorado. In this newly diagnosed HIV-infected cohort, linkage to care was slow and long-term retention in care was poor. Transitions between HIV care providers were common and may impair engagement in care over time. Out-of-state migration was frequent and may cause an underestimation of engagement in care.

Characteristics of foreign-born HIV infected individuals and differences by region of origin and gender.

To compare foreign-born (FB) and US-born (USB) patients (pts) in a US HIV care program. Retrospective review. Data were collected on all FB and a random sample of 5 % of USB pts in an HIV clinic in Colorado, USA. Comparisons were made between FB pts and USB pts and among FB pts by global region of origin and sex. Among 150 FB and 59 USB pts, FB pts were younger (40 vs. 45 years), proportionately more female (39 vs. 17 %), with heterosexual sex as HIV risk factor (69 vs. 23 %) and reported substance use less (6 vs. 38 %) (All p ≤ 0.001) compared to USB pts. Age and substance differences persisted between FB and USB women. Significant differences also existed between FB and USB pts in reason for HIV test, tuberculosis and mental health diagnoses, and diagnosis of >1 co-morbidity, but not in mean CD4 cell count (502 vs. 569), antiretroviral therapy (ART) (92 vs. 90 %), or alcohol use (29 vs. 37 %). Compared to FB women, FB men were more commonly men that have sex with men, from Latin America/Caribbean, have HIV testing for illness, and have had a concomitant HIV and AIDS diagnosis while FB women were more commonly refugees, heterosexual and from Africa. Differences exist between FB and USB HIV-infected pts, and among FB pts themselves. HIV care and prevention programs must recognize and address these dissimilarities in order to maximize clinical outcomes, improve linkage to and continuity in care and optimize resource allocation.

The frequency of adjusted renal dosing of tenofovir DF and its effects on patient outcomes.

Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus (HIV) and hepatitis B, is renally eliminated and has been associated with renal toxicities. Dose adjustments are recommended for patients with creatinine clearance (CrCL) <50 mL/min. We retrospectively determined the frequency in which HIV clinic providers adjusted TDF doses in patients with CrCL <50 mL/min over a 2-year period and compared clinical outcomes in patients who had TDF dose adjustments based on CrCL <50 mL/min versus those who did not. Thirty-nine patients with CrCL <50 mL/min were identified. Dose-adjusted patients (N = 9) continued their TDF-based antiretroviral regimens for 21 months longer following the first CrCL < 50 mL/min (P = .0193) and had gains in CD4 cell counts over 12 months (P = .0009). There were no statistically significant differences in CrCL or percentage of patients with detectable HIV-1 RNA at 6 and 12 months following first CrCL <50 mL/min in those who did versus did not have a TDF dose adjustment. In summary, HIV providers often failed to dose-adjust TDF in patients with CrCL <50 mL/min, but dose-adjusted patients appeared to stay on their TDF-based regimens longer and have greater gains in CD4 cells. Larger, prospective studies are needed to validate these results.

Enhancement of alkaline phytase production in Pichia pastoris: influence of gene dosage, sequence optimization and expression temperature.

Supplementation of animal feed with phytases has proven to be an effective strategy to alleviate phosphorous contamination of soil and water bodies. The inability of non-ruminant animals to digest phytates in corn and soybeans contributes to environmental contamination. Alkaline phytase from lily pollen (LlALP) exhibits unique catalytic and thermal stability properties that could be useful as a feed supplement. rLlALP2 was successfully expressed in Pichia pastoris; however, enzyme yields were modest (8-10 mg/L). In this paper, we describe our efforts to enhance rLlALP2 yield by investigating the influence of the following potential limiting factors: transgene copy number, codon bias, sequence optimization, and temperature during expression. Data presented indicate that increasing rLlAlp2 copy number was detrimental to heterologous expression, clones with one copy of wt-rLlAlp2 produced the highest activity, clones with two, four and seven or more copies produced 70%, 25% and 10% respectively, of enzyme activity implying that gene dosage is not limiting rLlALP2 yield. Use of a sequence-optimized rLlAlp2 increased the yield of the active enzyme by 25-50% in one/two copy clones, suggesting that translational efficiency is not a major bottleneck for rLlALP2 expression. Reducing the temperature during heterologous expression led to increases of 1.2-20-fold suggesting that protein folding and post-translational processes may be the dominant factors limiting rLlALP2 expression. Early knowledge of the transgene copy number allowed us to develop a more rational strategy for yield enhancement. Cumulatively, sequence optimization and temperature reduction led to the doubling of rLlALP2 enzyme activity in P. pastoris.